Surface erodible systems

Fig. 6. Mechanism of drug release from (a) homogenous, surface-eroding system, and...

To be useful as an implant, the polymer must hydrolyze to small, water soluble and toxicologically safe molecules and to be useful as a surface-eroding system, the hydrolysis must occur at much higher rates in the outer layers than it does in the bulk. Therefore, the successful development of such devices requires the selection of bonds that are capable of undergoing rapid hydrolysis. Two such bonds are anhydrides which are rapidly hydrolyzed to diacids even at the physiological pH of 7.4 and ortho esters which at pH 7.4 are slow to hydrolyze but which hydrolyze at increasingly rapid rates as the pH is lowered. Polymers based on both of these linkages are under intensive development and this chapter will cover, in depth, the development and current status of poly (ortho esters). 

When describing erosion of and drug release from surface erodible polymers, it is often implicitly assumed that the matrix erodes uniformly, thus resulting in a uniform release profile for a homogenously dispersed drug. While this may be a valid assumption for some homopolymer systems, neglecting the effects of crystallinity, some multicomponent... 

The past two decades have produced a revival of interest in the synthesis of polyanhydrides for biomedical applications. These materials offer a unique combination of properties that includes hydrolytically labile backbone, hydrophobic bulk, and very flexible chemistry that can be combined with other functional groups to develop polymers with novel physical and chemical properties. This combination of properties leads to erosion kinetics that is primarily surface eroding and offers the potential to stabilize macromolecular drugs and extend release profiles from days to years. The microstructural characteristics and inhomogeneities of multi-component systems offer an additional dimension of drug release kinetics that can be exploited to tailor drug release profiles. 

Surface erodible matrix systems. The first system is a solid matrix that does not disintegrate nor swell during dissolution but dissolves from the surface that is exposed to a dissolution medium. In this case, the drug is released from the eroding surface, and the dissolution profile simply... 

FIGURE 8 Theoretical controlled release from a surface-eroding polymeric system. (Adapted from ref. 93 with permission of Elsevier Copyright 1999.)... 

Heller and colleagues at Advanced Polymer Systems (Redwood City, CA) continue to develop additional polyorthoesters with a variety of physical properties and potential applications. ° Generally speaking, polyorthoesters do possess the potential to exhibit surface-eroding behavior. However, several issues that may limit the commercial application of this class of polymers are still present. One issue is that synthesis of these polymers involves complicated monomers and polymerization chemistry. The second issue is, to date, the toxicology and biocompatibility of these polymers and their degradation products have not yet been fully characterized. Finally, the requirement for pH-regulating additives such as acids and bases... 

Fig. 5 Eroding system with hollow cylinder and coated surfaces. (From Ref. f)...

Because surface erosion results in constant and predictable rate of drug release, this type of erosion is clearly preferrable to bulk erosion. However, to achieve surface erodibility, a system must be devised in which the rate of polymer degradation at the surface of a device is very much faster than the rate of degradation in the interior. 

Figure 18.18 Drug delivery from biodegradable systems, (A) surface eroding biodegradable system, (B) bulk eroding system [38].

LI3 Liu, Y., Kemmer, A., Keim, K., Curdy, C., Petersen, H., Kissel, T., Poly(ethylene carbonate) as a surface-eroding biomaterial for in situ forming parenteral drag delivery systems A feasibility study, Eur. J. Pharmaceut. Biopharmaceut, 76, 222, 2010. 

Kluin, O.S., et al. 2009. A surface-eroding antibiotic dehvery system based on poly-(trimethylene carbonate). Biomaterials 30(27) 4738-4742. 

The major difficulty in developing such a system is the requirement of surface erodibility to achieve this, the hydrolytic erosion process at the surface of the device must occur at a very much faster rate than the hydrolytic erosion process in the matrix interior. To develop such a system we have synthesized polymers that contains linkages in the pol mier backbone that are very labile... 

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